Purpose:
Electrical stimulation of the lacrimal gland is a promising new approach to increase tear production and provide relief to patients afflicted by dry eye disease. Delivery of electrical pulses, via wirelessly powered implant, stimulates nerves and increase tear secretion. We assessed efficacy of stimulation and safety of implantation in rabbits.

Methods:
New Zealand White rabbits were anesthetized and a wirelessly powered implantable stimulator was placed beneath the inferior lacrimal gland. In addition, platinum wire electrodes connected to a second stimulator placed subcutaneously above the orbit, were inserted through the posterior supraorbital foramen to target ocular sensory nerve fibers. The baseline and stimulated tear production were measured using the Schirmer test with topical proparacaine. During the five minute tear secretion measurements the implanted devices supplied asymmetric, charge-balanced, biphasic pulses of current (~1ms duration per phase, ~2.8mA) at 30Hz repetition rate. One protocol used 1 second long bursts of such pulses separated by 1 second without a stimulus; the other was an uninterrupted train of pulses. Tear osmolarity was measured using the TearLab® osmometer. After 5-7 months the animals were euthanized and the glands excised for histological analysis.

Results:
Electrical stimulation of the lacrimal gland with bursting stimulus resulted in a Schirmer score increase of 3.7 ± 0.6 mm above baseline, or approximately 40%. Uninterrupted stimulation produced a similar effect: 3.7 ± 0.8 mm, but not in every animal. The supraorbital stimulation increased the Schirmer score to 12.7 ± 1.0 mm above baseline, a 100% increase, but not in every animal. Tearing responses were elicited by stimulation throughout the duration of the study. Stimulated tears had 3% lower osmolarity, compared to baseline, but the difference was not statistically significant. Histology demonstrated absence of damage to the lacrimal gland after 5-7 months of implantation with intermittent stimulation.

Conclusions:
A chronically implanted electrical stimulator can safely and effectively stimulate the lacrimal gland for at least 5-7 months, providing increased tear production of about 40%. The supraorbital stimulation provided a 100% increase in tear volume. Cases where animals did not respond to stimulation indicate the importance of a precise implant placement relative to the targeted nerves and gland tissue.